Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival

TY - JOUR

T1 - Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival

AU - Nielsen, Rasmus H

AU - Karsdal, Morten A

AU - Sørensen, Mette G

AU - Dziegiel, Morten Hanefeld

AU - Henriksen, Kim

PY - 2007/9/7

Y1 - 2007/9/7

N2 - Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteoclast numbers, indicating increased life span of the osteoclasts. To investigate the role of the inorganic phase of bone with respect to osteoclast life span, we used the V-ATPase inhibitor bafilomycin and the calcium uptake antagonist ryanodine on human osteoclasts cultured on calcified and decalcified bone slices. Bafilomycin inhibited bone resorption and increased osteoclast survival on calcified but not decalcified bones. Ryanodine attenuated calcium uptake and thereby augmented osteoclast survival on calcified bones. In summary, we found that acidification leading to calcium release from bone during resorption controls osteoclast survival, potentially explaining the increased numbers of osteoclasts in patients with osteopetrosis.

AB - Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteoclast numbers, indicating increased life span of the osteoclasts. To investigate the role of the inorganic phase of bone with respect to osteoclast life span, we used the V-ATPase inhibitor bafilomycin and the calcium uptake antagonist ryanodine on human osteoclasts cultured on calcified and decalcified bone slices. Bafilomycin inhibited bone resorption and increased osteoclast survival on calcified but not decalcified bones. Ryanodine attenuated calcium uptake and thereby augmented osteoclast survival on calcified bones. In summary, we found that acidification leading to calcium release from bone during resorption controls osteoclast survival, potentially explaining the increased numbers of osteoclasts in patients with osteopetrosis.

KW - Apoptosis

KW - Bone and Bones

KW - Calcium

KW - Cell Survival

KW - Cells, Cultured

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Osteoclasts

U2 - 10.1016/j.bbrc.2007.06.145

DO - 10.1016/j.bbrc.2007.06.145

M3 - Journal article

C2 - 17631274

SN - 0006-291X

VL - 360

SP - 834

EP - 839

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -